D.B.A. Silk

PROSPECTIVE CONTROLLED TRIAL OF INJECTION SCLEROTHERAPY IN PATIENTS WITH CIRRHOSIS AND RECENT VARICEAL HÆMORRHAGE

64 patients with cirrhosis and recent variceal haemorrhage were studied in a prospective randomised trial of injection sclerotherapy by means of a flexible oesophageal sheath. 12 (33%) of the 36 patients in the sclerotherapy group, suffered further bleeds from varices compared with 19 (68%) of the 28 patients receiving standard medical treatment. The risk of bleeding per patient-month of follow up decreased more than threefold with sclerotherapy and the number of patients rebleeding after 2, 6, and 12 months was significantly reduced (p < 0.05). 1-year survival without further bleeding improved significantly with sclerotherapy (46% compared with 6%, p < 0.02), although the difference in overall survival assessed by cumulative life-table analysis was not statistically significant. The main complication of the technique was the development of oesophageal ulcers in some patients.

TREATMENT OF FULMINANT HEPATIC FAILURE BY POLYACRYLONITRILE-MEMBRANE HÆMODIALYSIS

24 patients with fulminant hepatic failure who had deteriorated to grade-IV coma were treated by repeated periods of haemodialysis with a polyacrylonitrile membrane. 9 patients fully recovered consciousness, and 8 (33%) survived to leave hospitals. These results are to be compared with those of conservative management alone (15% survival in 53 cases) and those obtained initially with charcoal haemo-perfusion (38%). Of the 16 treatment failures, cerebral oedema was found at necropsy in 13 (18%). Whether this would have been less of problem if treatment had been started earlier in the course of the illness remains to be determined.

Fulminant hepatic failure in childhood An analysis of 31 cases

To document the clinical features and complications of fulminant hepatic failure in childhood, 31 consecutive cases (of whom only 9 survived) were reviewed. Of 26 children with acute hepatitis (HbSAg-negative), liver function steadily deteriorated in all but 2, and encephalopathy occurred within 3 weeks of the onset of symptoms in all except 3 of them. Eight of these patients survived, as did one of 3 in which this deterioration was caused by paracetamol overdosage. Single cases due to Amanita phalloides and halothane died. Encephalopathy lasted from 2 to 16 days in the survivors, and from one to 20 days in the fatal cases. The severity fluctuated by more than one grade in 9 patients. The outcome was not related to the age or sex of patient, clinical or biochemical abnormalities at presentation, or to the duration of the encephalopathy. Prothrombin time was prolonged by more than 90 seconds in 10 fatal cases, but in none of the survivors. The outcome was related to the severity of the encephalopathy, only one (6%) of 19 children in grade 4 coma surviving, and to the occurrence of neurological complications—particularly brain stem dysfunction (9 cases), decerebrate posturing (12 cases), and convulsions (7 cases). Massive gastrointestinal bleeding (14 cases) and renal failure (10 cases) were confined to the fatal group. At necropsy 7 (54%) of 13 had cerebral oedema. Hypoglycaemia, septicaemia, respiratory tract infections, ascites, and haemopoietic complications occurred both in fatal cases and survivors. Although liver function tests and liver biopsy appearances remained abnormal in survivors for 24 and 30 months respectively, these children developed normally without evident disease during or after this period. Children with fulminant hepatic failure and severe encephalopathy develop major pathophysiological complications affecting almost every system. Such complications must be prevented or vigorously treated. The mortality is no lower than in adults. Effective treatment must be instituted before grade 4 coma is established.

Intracranial Pressure In Pigs with Surgically Induced Acute Liver Failure

Cerebral edema has now been noted to occur frequently in patients dying of fulminant hepatic failure. In the present study, intracranial pressure was monitored in an animal model of acute liver failure. Acute liver failure was induced surgically by hepatic devascularization. Serial monitoring of the electroencephalogram revealed progressive slowing of the frequency with decreasing amplitude. Elevation of the blood ammonia was also observed from baseline values of 64 +/- 12 SE to 744 +/- 97 mumol/liter. Monitoring of the intracranial pressure with a subdural pressure transducer demonstrated a progressive and reproducible rise from 12.8 +/- 2.5 mm Hg immediately after the operation to a mean value of 51.6 +/- 11.8 mm Hg just before death 6--12 hr later. At autopsy, the brains of the test animals were found to be swollen with flattened cortical gyri. In the control animals, intracranial pressure rose slightly but returned toward normal levels (8.0 +/- 2.5 mm Hg) 8 hr after laparotomy and remained normal until their death. There was a statistically significant difference between intracranial pressure levels of the test animals and those of the controls (P less than 0.01). Intravenous methylprednisolone (2.0 g initially followed by 0.5 g every 2 hr) administered immediately before and after hepatic devascularization prevented rises in intracranial pressure but had no effect when given 4 hr after operation. The early and progressive increase in intracranial pressure was an unexpected finding, and an assessment of such a sequence in patients with fulminant hepatic failure is currently in progress.

Plasma short-chain fatty acids in fulminant hepatic failure.

The role of short-chain fatty acids in the pathogenesis of coma in patients with fulminant hepatic failure has been studied by gas-liquid chromatography. There was no correlation between the initial or the final plasma levels of short-chain fatty acids in these patients and the clinical outcome of their disease. A primary role for the short-chain fatty acids in the pathogenesis of coma in fulminant hepatic failure is unlikely.

Treatment of Fulminant Hepatic Failure by Charcoal Haemoperfusion and Polyacrilonitrile Haemodialysis

Despite the considerable regenerative capacity of the liver, mortality from fulminant hepatic failure is as high as 80% in most reported series (1–3). Few of the patients who recover develop cirrhosis, however (4), and it is for this reason that a temporary means of liver support has been sought to tide these patients over the acute phase of their illness.

The effect of prostaglandin E1 and adenosine on adverse platelet reactions during charcoal haemoperfusion.

Abstract Severe side-effects, including irreversible hypotension, platelet losses, and rises in Swank screen filtration pressure have been observed during the use of charcoal haemoperfusion in patients with fulminant hepatic failure. In the present study we have been able, using a previously developed in vitro test circuit, to reproduce the rises in Swank screen filtration pressure. Scanning electron microscopy of the Swank filters has demonstrated that the rises were due to platelet aggregates in the blood. Addition of Prostaglandin E1 to the blood, adsorption of Prostaglandin E1 to the charcoal, or constant infusion of Adenosine into the blood just prior to the charcoal column were all able to inhibit in vitro the rises in Swank screen filtration pressure.